Lymphocyte infiltration and activation in iris-ciliary body and anterior chamber of mice in corneal allograft rejection

AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS: In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n=25). Grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4(+) T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS: Rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4(+) T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adhered to the corneal endothelium. Blood vessels in iris increased and were filled with lymphocytes. And lymphocytes were detected to migrate through endothelial cell gap out of vessels. When allograft rejection occurred, macrophages attached to endothelial cells with large number of lymphocytes and macrophages infiltrating in iris. CONCLUSION: Lymphocyte infiltration and activation occurred in iris-ciliary body after allogenic PK, and the lymphocytes could migrate from iris blood vessel to the anterior chamber, which might play an important role in corneal allograft immune rejection.

Role of biliary complications in chronic graft rejection after living donor liver transplantation

Postoperative biliary complications remain a substantial challenge after living donor liver transplantation,especially due to its heterogeneous clinical presentation.

Preservation of donor's heart and lung and discrimination and postoperative immunotherapy of graft rejection:a report of 2 cases of heart-lung transplantation

Objective To summarize preservation measures of donor’s heart and lung,and postoperative imrnunotherapy,as well as clinical experience of discrimination and management for graft rejection. Methods Clinical data of 2 cases of heart - lung transplantation in our depart-

Hepatic allograft rejection after liver transplantation: Clinicopathological debates

Liver transplantation(LT)represents a life-saving surgical procedure and is considered the current standard of care for the majority of patients having end-stage liver disease.As known,significant progress in organ preservation techniques,perioperative care,and strict immunosuppression protocols are associated with favorable patient/graft survival post-LT.Hence,proper evaluation of liver allograft-related complications among survivors has paid great attention,particularly the rejection sequel after LT.It is a seriously underestimated cause of allograft injury,which pushes researchers for understanding the exact pathogenesis of different types and proper time diagnosis for better management of such complications.However,it still represents a challenge because of the complexities related to diagnosis and histopathology.Hence,increasing clinical awareness with earlier diagnosis of post-LT rejection is essential through stimulating further studies.Therefore,our review will focus on the clinicopathological debates regarding liver allograft loss after transplantation.

Delayed allogeneic skin graft rejection in CD26-deficient mice

Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by,for example,preventing transplant rejection.In the current study,CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4(DPPIV)in allogeneic skin graft rejection by tail-skin transplantation.Compared with wild-type(CD26^(+/+))counterparts,CD26^(-/-)mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation.Concentrations of serum IgG,including its subclasses IgG1 and IgG2a,were significantly reduced in CD26^(-/-)mice during graft rejection.Moreover,after allogeneic skin transplantation,the secretion levels of the cytokines IFN-γ,IL-2,IL-6,IL-4,and IL-13 were significantly reduced,whereas the level of the cytokine IL-10 was increased in the serum of CD26^(-/-)mice compared with that in the serum of CD26^(+/+)mice.Additionally,the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes(MPBLs)were both significantly lower,while the percentage of regulatory T cells(Tregs)was significantly higher in MPBLs of CD26^(-/-)mice than in those of CD26^(+/+)mice.Furthermore,a lower percentage of CD8^(+)T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26^(-/-)mice were detected during graft rejection.These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.

Donor liver natural killer cells alleviate liver allograft acute rejection in rats

BACKGROUND:Liver enriched natural killer (NK) cells are of high immune activity.However,the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear.METHODS:Ten Gy of whole body gamma-irradiation (WBI) from a 60 Co source at 0.6 Gy/min was used for depleting donorderived leukocytes,and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells,dtl NKs) through portal vein was performed immediately after grafting the irradiated liver.Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients’ survival in rat LTx.RESULTS:Transfusion of dtl NKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx,but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat).Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes,better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtl NKs.CONCLUSIONS:Donor liver NK cells alone do not exacerbate liver allograft acute rejection.Conversely,they can alleviate it,and improve the recipients’ survival.

Roles of interleukin-10 in acute graft-versus-host disease and graft rejection

To study the role of interleukin(IL)-10 in acute-graft-versus-host disease (aGVHD) and graft rejection Methods Serum concentrations of IL-10 in 28 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were measured by enzymed-linked immunosorbent assay (ELISA) IL-10 gene expression in peripheral mononuclear cells was measured by reverse-transcriptase polymerase chain reaction (RT-PCR) after transplantation Results Seven patients developed grade Ⅰ GVHD, 7 patients developed grade Ⅱ-Ⅳ GVHD, 4 patients had graft rejection Before transplantation, the concentrations of IL-10 were higher in patients who later did not developed aGVHD After transplantation, IL-10 levels increased in patients without aGVHD, but decreased in patients with aGVHD or graft rejection And IL-10mRNA was more frequent in patients without aGVHD compared to those with aGVHD Conclusions IL-10 plays a negative role in the development of aGVHD and graft rejection

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.

High-risk corneal allografts: A therapeutic challenge

Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in "low-risk" settings. Furthermore, although corneal graft survival in "lowrisk" recipients is favourable, the prognosis in "high-risk" recipients for corneal graft is poor. In "high-risk" grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of "high-risk" recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in "high-risk" recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicinemay be able to solve both important short comings of allotransplantation:(1) graft rejection and ultimate graft failure; and(2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide problem of corneal blindness in both "low-risk" and "high-risk" hosts.

Immunological tolerance of human hepatocyte xenograft induced by adenovirus vector-mediated CTLA4Ig gene transfer

BACKGROUND:Systemic administration of CTLA4Ig has been applied in inducing immunological tolerance of hepatocyte implants,but has potential for systemic immune inhibition.This study was designed to induce hepatocyte immunological tolerance by locally expressing CTLA4Ig in an attempt to improve the effectiveness of cell transplantation.METHODS:A normal human liver cell line(L02) was transfected with adenovirus vector containing the CTLA4Ig gene(Ad-CTLA4Ig-EGFP) in vitro,and the expression of CTLA4Ig by transfected cells was assessed by fluorescent imaging and immunocytochemical staining.Transfected cells then were injected into the spleen of Sprague-Dawley rats,the survival of cells was determined by immunohistochemistry,and the immune status was examined through CD4 + and CD69 + T cellcounts and ELISA detection of IL-2 in peripheral blood.RESULTS:L02 cells expressed CTLA4Ig in the cytoplasm for >4 weeks.Surviving L02 cells were observed in the experimental group at 3 and 4 weeks post-transplantation,while none was detected in the control group.Furthermore,the percentages of CD4 + and CD4 + CD69 + T cells in the CTLA4-transfected group were 24.5% and 45.1%,markedly lower than those in the control group at 4 weeks post-transplantation(P<0.01).Furthermore,the IL-2 level was also lower in the CTLA4transfected group than in the control group.CONCLUSION:Adenovirus-mediated CTLA4Ig gene transfer into human hepatocytes has the potential to become an effective method of inducing immunological tolerance in hepatocyte transplantation.

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIM To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODS We performed a retrospective analysis of 123 pediatric liver transplantation(LT)recipients who participated in yearly follow-ups including Luminex testing for DSA at our center.The cohort was split into two groups according to the DSA status(DSA-positive n=54,DSA-negative n=69).Groups were compared with regard to liver function,biopsy findings,graft survival,need for re-LT and immunosuppressive medication.RESULTS DSA-positive pediatric patients showed a higher prevalence of chronic rejection(P=0.01),fibrosis(P<0.001)and re-transplantation(P=0.018)than DSA-negative patients.Class II DSAs particularly influenced graft survival.Alleles DQ2,DQ7,DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis.Mean fluorescence intensity levels and DSA number did not impact graft survival.Previous episodes of chronic rejection might lead to DSA development.CONCLUSION DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT.Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibodymediated rejection improved early identification of patients at risk of graft loss.

Graft Intolerance Syndrome in Children Treated with Kidney Embolization: A Case Report

During post-transplant evolution, adolescents may present problems with adherence to treatment, becoming a high-risk group for graft loss. Here, we report a case which describes an adolescent patient who lost a graft due to humoral rejection associated with lack of adherence to treatment. During chronic peritoneal dialysis therapy, the patient developed pain and increased volume in the graft area, fever, gross hematuria and leukocyturia upon urine examination. The patient was diagnosed with graft immune intolerance syndrome and transplantectomy was suggested. Finally, a graft embolization was performed. A decrease in symptoms was observed until the patient became asymptomatic.

Mycophenolate Mofetil with Low Dose CsA for Chronic Rejection in Primary Cadaveric Renal Recipients

Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5~2.0 g/d+ CsA 2 to 3 mg/kg·d -1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.

Islet transplantation-immunological challenges and current perspectives

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

Outcome of Renal Transplantation at Ahmed Gasim Cardiac and Renal Transplant Centre in Sudan-2014

Background: Although not life-saving procedures like liver or heart transplantation, renal transplantation is the preferred treatment for many patients with end-stage renal disease because it improves patients’ quality of life, while other forms of renal replacement therapy (RRT) such as haemodialysis (HDX) shown to regain only 10% of the patient’s renal function [1]. Transplantation releases patients from the dietary and fluid restrictions and the physical constraints imposed by other forms of (RRT), patients become able to return to their normal activities. Patient’s 5-year survival is higher post transplant. Patients and methods: This is Descriptive, retro-prospective, cross sectional analytic and multicentre study done in Ahmed Gasim Cardiac and Renal Transplant Centre including 105 patients. After meeting the Inclusion Criteria and exclusion Criteria, then cases were selected and written in constructed questionnaire. The aim of the study was to evaluate the outcome of renal transplantation in Sudan. Results: 105 cases were used with male predominate and ratio male to female ratio 3:1, the main age of presentation between 31 - 45 years, most of the patients discharge uneventful with good outcome. During one-year follow-up following renal transplantation. Patient survival 95.2 % graft survival 82.4%. Overall morbidity shows 70.5%. Conclusion: this study showed that the one-year patient survival of 95.2%. Actuarial one-year graft survival of 92.4%. Renal transplantation complications can be reduced by meticulous preoperative workup including good cardiovascular assessment, tissue mismatch and BMI good postoperative follow up for early detection of graft rejection and long-term complications and finally patient education.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

The critical role of therapeutic plasma exchange in ABO-incompatible liver transplantation

Background:The shortage of donor liver restricts liver transplantation(LT).Nowadays,donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor liver.Although it is now possible to perform ABO-incompatible(ABO-I)LT,antibody-mediated rejection(AMR)has been recognized as the primary cause of desperate outcomes after ABO-I LT.Anti-A/B antibody is the trigger of immune response to ABO-I LT graft injury.Therapeutic plasma ex-change(TPE)can quickly reduce the titer of plasma antibodies and effectively inhibit humoral immunity.Data sources:We searched PubMed and CNKI databases using search terms“therapeutic plasma ex-change”,“ABO-incompatible liver transplantation”,“ABO-I LT”,“liver transplantation”,“LT”,“antibody-mediated rejection”,and“AMR”.Additional publications were identified by a manual search of references from key articles.The relevant publications published before September 30,2020 were included in this review.Results:Different centers have made different attempts on whether to use TPE,when to use TPE and how often to use TPE.However,the control standard of lectin revision level is always controversial,the target titer varies significantly from center to center,and the standard target titer has not yet been estab-lished.TPE has several schemes to reduce antibody titers,but there is a lack of clinical trials that provide standardized procedures.Conclusions:TPE is essential for ABO-I LT.Hence,further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

Biliary complications in recipients of living donor liver transplantation:A single-centre study

BACKGROUND Biliary complications(BCs)after liver transplantation(LT)remain a considerable cause of morbidity,mortality,increased cost,and graft loss.AIM To investigate the impact of BCs on chronic graft rejection,graft failure and mortality.METHODS From 2011 to 2016,215 adult recipients underwent right-lobe living-donor liver transplantation(RT-LDLT)at our centre.We excluded 46 recipients who met the exclusion criteria,and 169 recipients were included in the final analysis.Donors’and recipients’demographic data,clinical data,operative details and postoperative course information were collected.We also reviewed the management and outcomes of BCs.Recipients were followed for at least 12 mo post-LT until December 2017 or graft or patient loss.RESULTS The overall incidence rate of BCs including biliary leakage,biliary infection and biliary stricture was 57.4%.Twenty-seven(16%)patients experienced chronic graft rejection.Graft failure developed in 20(11.8%)patients.A total of 28(16.6%)deaths occurred during follow-up.BCs were a risk factor for the occurrence of chronic graft rejection and failure;however,mortality was determined by recurrent hepatitis C virus infection.CONCLUSION Biliary complications after RT-LDLT represent an independent risk factor for chronic graft rejection and graft failure;nonetheless,effective management of these complications can improve patient and graft survival.

Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation

BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.

Factors affecting complications development and mortality after single lung transplant

Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.